Glucocorticoids and the prenatal programming of neurodevelopmental disorders

- Prenatal GC exposure can affect the risk of anxiety and depression.
- Prenatal GC exposure has variable consequences for different brain regions.
- The timing of the administration of synthetic GC is crucial for any later effects.
- Epigenetic changes in genes involved in brain function may be important.

Synthetic glucocorticoids are frequently used antenatally in order to reduce morbidity and mortality in babies born preterm and have been used in the management of fetuses known to be at risk of congenital adrenal hyperplasia. Although such treatment has short term advantages, evidence suggests that it can affect health in later life. Several studies have reported negative consequences of prenatal exposure to the synthetic glucocorticoid dexamethasone on offspring behavior in humans and in animal models, in association with changes in brain structure, hypothalamic-pituitary-adrenal axis function, neurotransmitter pathways, gene transcription and epigenetic regulation. These studies also highlight the importance of timing and tissue/organ-specific and sex-specific effects of prenatal glucocorticoid exposure. Here we review the evidence from human and animal studies that links prenatal synthetic glucocorticoid exposure with an increased risk for neurodevelopmental disorders.